Negotiating the risks

Second breast cancers may be more difficult to treat in women who take the drug tamoxifen, study suggests

July 5, 2001

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By KRISTEN WOODWARD

Dr. Christopher Li displays the distinctive pill form of tamoxifen (with a sculpted silhouette of a woman's head), which his recent study finds has mixed results in preventing breast cancer - a decreased risk of second breast cancer but increased risk of more-difficult-to-treat cancer in the opposite breast.

Photo by Clay Eals

A new Hutch study confirms that tamoxifen use decreases the risk of a second breast cancer, but it also finds that the drug may cause a fivefold increased risk of estrogen-receptor (ER)-negative breast cancer - a cancer that is more difficult to treat - in the breast opposite, or contralateral, to the initial tumor.

The study follows research in recent years indicating tamoxifen improves survival and reduces risk of recurrence among women diagnosed with breast cancer.

Dr. Christopher Li, and colleagues in the Public Health Sciences Division reported their findings yesterday in the Journal of the National Cancer Institute. The population-based study was funded by a grant from the Life Possibilities Fund.

500-percent increase

Comparing breast-cancer patients who received tamoxifen to those who did not, Li and colleagues found that while the drug appeared to cause a 20 percent reduction in ER-positive contralateral breast cancer - the more common type - it also appeared to increase the risk of ER-negative contralateral tumors by nearly 500 percent.

"Among women who take tamoxifen after an initial breast-cancer diagnosis, our study and numerous random trials suggest that tamoxifen will decrease a woman's risk of developing cancer in the other breast," Li said.

"But if they do develop a tumor on the opposite side, our study suggests that the cancer is more likely to be ER negative, which is associated with a higher mortality risk."

Li and colleagues' data analysis showed that 27 percent of the contralateral tumors that developed in tamoxifen users were ER negative, while only 4 percent of the contralateral tumors that developed in non-users were ER negative.

Caution about advice

A postdoctoral fellow in epidemiology at the Hutchinson Center and at the University of Washington School of Public Health and Community Medicine, Li cautioned that the study shouldn't alter what physicians recommend to their patients.

"While this study, if confirmed by others, adds to our knowledge about the effects of tamoxifen, I do not believe it should change current clinical practices, as tamoxifen has clearly been shown to reduce the risk of recurrence and improve survival among women diagnosed with breast cancer," he said.

The majority of breast tumors - about two thirds of those initially diagnosed - are ER positive, which means they need the hormone estrogen to grow. Such tumors respond well to anti-estrogen drugs, such as tamoxifen, which block the receptor, or docking site, to which estrogen can bind, thereby halting the growth of cancer cells.

ER-negative tumors, on the other hand, can thrive without estrogen and are therefore unresponsive to estrogen blockers such as tamoxifen.

Besides being more difficult to treat, ER-negative tumors are associated with a higher mortality rate. Women with this type of breast cancer face an 8 to 35 percent lower five-year survival rate than those whose tumors are ER positive.

The study population involved nearly 9,000 women in western Washington diagnosed between 1990 and 1998 with primary localized or regional-stage cancer in one breast. The women, 50 years or older, were followed until cancer developed in the other breast, they died or the study ended in December 1999.

Overall, among the tamoxifen users, 89 developed cancer in the opposite breast. Among non-users, 100 developed a tumor on the other side.

Study data was obtained from the Hutch Cancer Surveillance System, a population-based registry of cancer incidence in western Washington.

This is the first population-based study of its kind to address the estrogen-receptor status of contralateral breast tumors among women who have used tamoxifen in the treatment of their breast cancer, said Dr. Janet Daling, senior author of the paper.

"Future studies should further evaluate the characteristics of contralateral tumors among women who do and do not receive tamoxifen treatment to increase our understanding of the mechanisms involved," said Daling of the Hutch PHS division and a professor of epidemiology at the UW School of Public Health and Community Medicine.

Risks associated with tamoxifen use include an increased risk of endometrial cancer, deep-vein thrombosis (blood clots), pulmonary embolism and cataracts.

Benefits linked with tamoxifen include a reduced risk of breast-cancer recurrence and improved survival, reduced risk of bone fractures and a lowering of LDL, or "bad," cholesterol levels.

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